4-aminopyrimidines and their use for the antimicrobial treatment of surfaces

ABSTRACT

A method is provided for the antimicrobial treatment of a surface which comprises the contacting a surface with substituted 4-aminopyrimidines.

The present invention relates to substituted 4-aminopyrimidines, to the preparation of such compounds, and to the use of such compounds in the antimicrobial treatment of surfaces, as antimicrobial active substances against gram-positive and gram-negative bacteria, yeasts and fungi and also in the preservation of cosmetics, household products, textiles and plastics and for use in disinfectants.

The present invention relates to the use of 4-aminopyrimidines of formula

-   -   R₁ and R₂ are each independently of the other hydrogen;         C₁-C₅alkyl which is unsubstituted or substituted by one or more         halogen atoms; biphenyl or C₆-C₁₀aryl which is unsubstituted or         substituted by halogen, C₁-C₅alkyl, C₁-C₅alkoxy or by amino; a         5- to 7-membered heteroaryl radical; or cyclo-C₃-C₇alkyl;     -   R₃ is hydrogen; phenyl or C₁-C₅alkyl which is unsubstituted or         substituted by one or more halogen atoms;     -   R₄ is hydrogen; C₁-C₁₀alkyl; phenyl; or a 5- to 7-membered         heteroaryl radical;     -   R₅ is C₁-C₂₀alkyl which is unsubstituted or substituted by one         or more halogen atoms or by a heterocyclic radical or         interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; NR″R′″-C₁-C₁₀ alkyl which is unsubstituted or substituted by a heterocyclic radical or interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; cyclo-C₅-C₈alkyl; hydroxy-C₁-C₂₀alkyl; phenyl-C₁-C₃alkyl; a heterocyclic radical; or

-   -   R₄ and R₅, together with the nitrogen atom linking them, form a         radical of

-   -   R′ is hydrogen; or C₁-C₃alkyl;     -   R″ and R′″ are each independently of the other hydrogen;         C₁-C₅alkyl; or hydroxy-C₁-C₅alkyl;     -   X is

-   -   R″″ is hydrogen; C₁-C₄alkyl; or heteroaryl-C₁-C₄alkyl; and     -   n₁ and n₂ are each independently of the other from 1 to 8;         in the antimicrobial treatment of surfaces.

C₁-C₂₀Alkyl radicals are straight-chain or branched alkyl radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, amyl, isoamyl or tert-amyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl or eicosyl.

C₃-C₁₀Cycloalkyl denotes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl. Those radicals may be substituted, for example by one or more identical or different C₁-C₄alkyl radicals, especially by methyl, and/or by hydroxy. When cycloalkyl radicals are substituted by one or more substituents, they are substituted preferably by one, two or four, especially by one or two, identical or different substituents.

C₁-C₅Alkoxy radicals are straight-chain or branched radicals such as, for example, methoxy, ethoxy, propoxy, butoxy or pentyloxy.

C₆-C₁₀Aryl and heteroaryl radicals may be unsubstituted or may carry one or more, for example one, two, three or four, identical or different substituents, which may be located in any positions. Examples of such substituents are, for example, C₁-C₄alkyl, halogen, hydroxy, C₁-C₄alkoxy, trifluoromethyl, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, aminocarbonyl, amino, C₁-C₄alkylamino, di-C₁-C₄alkylamino and C₁-C₄alkylcarbonylamino.

Heteroaryl radicals are derived from heterocycles containing one, two, three or four identical or different ring hetero atoms, especially from heterocycles containing one, two or three, more especially one or two, identical or different hetero atoms. The heterocycles may be mono- or poly-cyclic, for example mono-, bi- or tri-cyclic. They are preferably mono- or bi-cyclic, especially monocyclic. The rings preferably contain 5, 6 or 7 ring members. Examples of monocyclic and bicyclic heterocyclic systems from which radicals occurring in the compounds of formula (1) can be derived are, for example, pyrrole, furan, thiophene, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyridazine, pyrimidine, pyrazine, pyran, thiopyran, 1,4-dioxane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, indole, benzothiophene, benzofuran, pyrrolidine, piperidine, piperazine, morpholine and thiomorpholine.

Unsaturated heterocycles may contain, for example, one, two or three unsaturated double bonds in the ring system. 5-membered rings and 6-membered rings in monocyclic and polycyclic heterocycles may also be, especially, aromatic.

Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

In accordance with the invention, preference is given to the use of compounds of formula (1) wherein

-   -   R₅ is R″R′″N—C₁-C₂₀alkyl which is uninterrupted or interrupted         by one or more —O— or

groups or by a bivalent heterocyclic radical;

-   -   R′ is hydrogen; or C₁-C₅alkyl;     -   R″ and R′″ are each independently of the other hydrogen; or         methyl; and     -   R₁, R₂, R₃ and R₄ are as defined for formula (1).

Very special preference is given to the use of compounds of formula (1) wherein

-   -   R₅ is R″R′″N—C₁-C₂₀alkyl which is uninterrupted or interrupted         by

In accordance with the invention, there are furthermore used compounds of formula (1) wherein

-   -   R₅ is R″R′″N—C₅-C₂₀alkyl which is uninterrupted or interrupted         by one or more —O— or

groups;

-   -   R′ is hydrogen; or C₁-C₅alkyl; and     -   R″ and R′″ are each independently of the other hydrogen; or         methyl.

Among those compounds, preference is given to those wherein

-   -   R₅ is R″R′″N—C₁-C₅alkyl; and     -   R″ and R′″ are each independently of the other hydrogen; or         methyl.

Very special preference is also given to the use of compounds of formula (1) wherein

-   -   R₄ is hydrogen; or C₁-C₅alkyl;     -   R₅ is C₅-C₂₀alkyl which is unsubstituted or interrupted by —NH—;         and     -   R₁, R₂ and R₃ are as defined for formula (1);     -   especially compounds of formula (1) wherein     -   R₁ is hydrogen; C₁-C₅alkyl; unsubstituted or         C₁-C₄alkyl-substituted phenyl or phenyl-C₁-C₄alkyl; or pyridino;     -   R₂ is hydrogen; or C₁-C₅alkyl; especially methyl;     -   R₃ is hydrogen; or C₁-C₅alkyl;     -   R₄ is hydrogen; or C₁-C₅alkyl; and     -   R₅ is C₅-C₂₀alkyl;     -   and very especially compounds of formula (1) wherein     -   R₁ is hydrogen; C₁-C₅alkyl, especially isopropyl or methyl;         unsubstituted or C₁-C₄alkyl-substituted phenyl; or pyridino;     -   R₂ is methyl;     -   R₃ and R₄ are hydrogen; and     -   R₅ is C₈-C₁₈alkyl.

Among the last-mentioned compounds very special preference is given to the use of those wherein

-   -   R₅ is linear C₈-C₁₈alkyl.

Also preferably used are compounds of formula (1) wherein, in formula (1a),

-   -   R″″ is hydrogen; or pyridyl-C₁-C₃alkyl; and     -   n₁ and n₂ are each 2.

Preference is also given to the use of compounds of formula (1) wherein

-   -   R₁ and R₂ are each independently of the other hydrogen;         C₁-C₅alkyl; phenyl which is unsubstituted or substituted by         halogen, C₁-C₅alkyl, C₁-C₅alkoxy or by amino; biphenyl;         cyclo-C₃-C₇alkyl; 3-pyridyl; 4-pyridyl; 2-thiophenyl;         3-thiophenyl; or thiazolyl;     -   or compounds of formula (1) wherein     -   R₃ is hydrogen; or phenyl;     -   or compounds of formula (1) wherein     -   R₄ is hydrogen.

Special preference is given to the use of compounds of formula

wherein

-   -   X is —O—; or

-   -   R′ is hydrogen; or C₁-C₃alkyl;     -   n is 1-3; and     -   m is 1-3;         and     -   R₁, R₂ and R₃ are as defined for formula 1.

The Table that follows lists, by way of example, further 4-aminopyrimidines according to the invention:

Comp. of Purity [%] Purity [%] formula Structural formula 254 nm 280 nm 3

64 72 4

37 96 5

83 97 6

92 97 7

43 48 8

82 93 9

94 98 10

49 59 11

75 89 12

95 97 13

94 99 14

91 97 15

91 98 16

42 44 17

39 43 18

42 51 19

64 70 20

63 77 21

70 82 22

51 65 23

67 82 24

95 97 25

88 96 26

81 90 27

88 93 28

86 93 29

61 62 30

85 72 31

45 42 32

69 64 33

94 93 34

89 89 35

92 88 36

82 73 37

82 66 38

56 34 39

67 46 40

43 44 41

81 77 42

91 92 43

72 68 44

88 84 45

82 83 46

88 88 47

72 67 48

81 85 49

92 84 50

84 86 51

77 73 52

88 91 53

87 89 54

90 91 55

85 87 56

87 84 57

99 99 58

58 78 59

34 64 60

46 32 61

90 87 62

66 61 63

99 95 64

80 80 65

96 92 66

90 95 67

48 44 68

37 38 69

64 79 70

71 82 71

88 88 72

79 52 73

90 96 74

79 39 75

92 89 76

97 95 77

86 90 78

90 94 79

92 95 80

54 50 81

40 42 82

67 84 83

77 72 84

93 91 85

83 80 86

92 92 87

95 94 88

94 95 89

92 90 90

54 33 91

89 95 92

52 48 93

40 39 94

65 80 95

82 83 96

78 85 97

31 26 98

79 60 99

93 90 100

71 59 101

87 78 102

49 25 103

89 89 104

54 41 105

33 38 106

65 75 107

80 82 108

87 96 109

87 87 110

90 94 111

94 92 112

87 90 113

92 85 114

41 28 115

93 96 116

58 46 117

39 40 118

54 70 119

82 87 120

42 35 121

87 90 122

78 87 123

68 73 124

93 96 125

93 93 126

87 86 127

65 69 128

46 52 129

58 69 130

82 83 131

73 74 132

88 90 133

94 93 134

100 89 135

92 91 136

92 92 137

49 44 138

41 41 139

50 66 140

100 80 141

74 71 142

100 83 143

84 79 144

62 54 145

43 39 146

34 35 147

61 73 148

72 70 149

91 89 150

87 88 151

88 86 152

91 83 153

89 85 154

94 85 155

85 81 156

86 82 157

62 63 158

86 92 159

89 91 160

88 92 161

87 92 162

67 88 163

67 66 164

85 92 165

81 92 166

68 75 167

92 89 168

72 73 169

87 83 170

77 85 171

86 81 172

87 72 173

69 67 174

66 87 175

69 64 176

82 57 177

87 92 178

77 69 179

77 85

The 4-aminopyrimidines used in accordance with the invention are prepared by methods known per se (J. Org. Chem.; 1967, 32, 1591). For that purpose, a cyano compound (R₁—C≡N) is reacted, in a suitable solvent such as, for example, methanol, ethanol, isopropanol, DMF, tetrahydrofuran etc., with ammonium acetate or ammonium chloride at a temperature of from −10° C. to 100° C. over a period of from 1 hour to 24 hours to form the corresponding amidine compound

The amidine compound is then condensed with an appropriate β-keto ester

using an auxiliary base such as, for example, sodium carbonate, potassium hydroxide, sodium ethanolate, sodium methanolate, potassium tert-butanolate etc., in a suitable solvent such as, for example, methanol, ethanol, butanol, tert-butanol, THF, DMF, acetonitrile, toluene, xylene etc., over a period of from 1 to 24 hours at a temperature of from 40 to 120° C.

The 4-hydroxy-2-pyrimidine compound

thereby obtained is then converted into the corresponding 4-chloro-2-pyrimidine compound

by conventional methods using phosphorus oxychloride.

The substituted 4-aminopyrimidines

are obtained by reacting the 4-chloro-2-pyrimidine compound with a primary or secondary amine (R₄R₅NH) in a suitable solvent such as, for example, DMF, dioxane, toluene, xylene, ethanol, butanol, and an auxiliary base such as, for example, triethylamine, DIEA, sodium carbonate, potassium hydroxide etc., or using an excess of amine at from 40 to 130° C. over a period of from 1 to 24 hours.

The entire reaction proceeds according to the following scheme:

R₁, R₂, R₃, R₄ and R₅ being as defined for formula (1).

Preparation of the compounds of formula (2) is carried out by reacting an excess of from 2 to 10 equivalents of the diamine compound H₂N(CH₂)_(n)X(CH₂)_(m)NH₂ in, for example, DMF, dichloromethane, THF or dioxane with trityl chloride polystyrene resin at a temperature of from 10 to 50° C. over a period of from 0.5 to 24 hours. From 2 to 10 equivalents of the appropriately substituted 4,6-dichloropyrimidines

are then reacted, in a suitable solvent such as, for example, dichloromethane, DMF, THF or toluene, with the polymer-bound diamines at from 10 to 120° C. over a period of from 2 to 48 hours. The 4-chloropyrimidines are reacted with from 2 to 10 equivalents of various boronic acids, from 1 to 10% of palladium catalyst and from 2 to 10 equivalents of auxiliary base such as, for example, CaCO₃ and NaCO₃, in, for example, THF, DMF or dioxane. After washing the resin to remove the excess, the target compounds are split off using from 1 to 30% trifluoroacetic acid (TFA) in dichloromethane (DCM) at 25° C. over a period of from 1 to 5 hours. For the purpose of further purification, the substances are freeze-dried from tBuOH/water 4:1 with from 1 to 10% HOAc and once from tBuOH/water 4:1.

The entire reaction proceeds according to the following scheme:

R₁, R₂, R₃, X, m and n being as defined for formula (2).

Some of the 4-aminopyrimidines used in accordance with the invention are known from the literature and some are novel compounds. The invention relates also to those novel compounds.

The novel compounds correspond to formula

-   -   R₁ and R₂ are each independently of the other hydrogen;         C₁-C₅alkyl which is unsubstituted or substituted by one or more         halogen atoms; biphenyl or C₆-C₁₀aryl which is unsubstituted or         substituted by halogen, C₁-C₅alkyl, C₁-C₅alkoxy or by amino; a         5- to 7-membered heteroaryl radical; or cyclo-C₃-C₇alkyl;     -   R₃ is hydrogen; phenyl or C₁-C₅alkyl which is unsubstituted or         substituted by one or more halogen atoms;     -   R₄ is hydrogen; C₁-C₁₀alkyl; phenyl; or a 5- to 7-membered         heteroaryl radical;     -   R₅ is C₁-C₂₀alkyl which is unsubstituted or substituted by one         or more halogen atoms or by a heterocyclic radical or         interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; NR″R′″-C₁-C₂₀alkyl which is unsubstituted or substituted by a heterocyclic radical or interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; cyclo-C₅-C₈alkyl; hydroxy-C₁-C₂₀alkyl; phenyl-C₁-C₃alkyl; a heterocyclic radical; or

-   -   R₄ and R₅, together with the nitrogen atom linking them, form a         radical of

-   -   R′ is hydrogen; or C₁-C₃alkyl;     -   R″ and R′″ are each independently of the other hydrogen;         C₁-C₅alkyl; or hydroxy-C₁-C₅alkyl;     -   X is

-   -   R″″ is hydrogen; C₁-C₄alkyl; or heteroaryl-C₁-C₄alkyl; and     -   n₁ and n₂ are each independently of the other from 1 to 8;     -   not including compounds of formula (1′) wherein simultaneously     -   R₁ is C₆-C₁₀aryl; or C₁-C₄alkyl; and     -   R₅ is C₁-C₇alkyl.

The 4-aminopyrimidines used in accordance with the invention exhibit pronounced antimicrobial action, especially against pathogenic gram-positive and gram-negative bacteria and against bacteria of the skin flora, and also against yeasts and moulds. They are accordingly suitable especially for disinfection, deodorisation, and for general and antimicrobial treatment of the skin and mucosa and of integumentary appendages (hair), more especially for the disinfection of hands and wounds.

They are accordingly suitable as antimicrobial active substances and preservatives in personal care preparations such as, for example, shampoos, bath additives, haircare preparations, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, e.g. cleansing solutions for the skin, moist cleaning cloths, oils or powders.

The invention accordingly relates also to a personal care preparation comprising at least one compound of formula (1) and cosmetically tolerable carriers or adjuvants.

The personal care preparation according to the invention contains from 0.01 to 15% by weight, preferably from 0.1 to 10% by weight, based on the total weight of the composition, of a compound of formula (1), and cosmetically tolerable adjuvants.

Depending upon the form of the personal care preparation, it comprises, in addition to the 4-aminopyrimidine of formula (1), further constituents such as, for example, sequestering agents, colorants, perfume oils, thickeners or solidifiers (consistency regulators), emollients, UV-absorbers, skin protective agents, antioxidants, additives that improve the mechanical properties, such as dicarboxylic acids and/or aluminium, zinc, calcium or magnesium salts of C₁₄-C₂₂fatty acids, and, optionally, preservatives.

The personal care preparation according to the invention may be in the form of a water-in-oil or oil-in-water emulsion, an alcoholic or alcohol-containing formulation, a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, a gel, a solid stick or an aerosol formulation.

As a water-in-oil or oil-in-water emulsion, the cosmetically tolerable adjuvant contains preferably from 5 to 50% of an oil phase, from 5 to 20% of an emulsifier and from 30 to 90% water. The oil phase may comprise any oil suitable for cosmetic formulations such as, for example, one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. Preferred mono- or poly-ols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.

Cosmetic formulations according to the invention are used in various fields. There come into consideration, for example, especially the following preparations:

-   -   skin-care preparations, e.g. skin-washing and cleansing         preparations in the form of tablet-form or liquid soaps,         synthetic detergents or washing pastes,     -   bath preparations, e.g. liquid (foam baths, milks, shower         preparations) or solid bath preparations, e.g. bath cubes and         bath salts;     -   skin-care preparations, e.g. skin emulsions, multi-emulsions or         skin oils;     -   cosmetic personal care preparations, e.g. facial make-up in the         form of day creams or powder creams, face powder (loose or         pressed), rouge or cream make-up, eye-care preparations, e.g.         eyeshadow preparations, mascaras, eyeliners, eye creams or         eye-fix creams; lip-care preparations, e.g. lipsticks, lip         gloss, lip contour pencils, nail-care preparations, such as nail         varnish, nail varnish removers, nail hardeners or cuticle         removers;     -   intimate hygiene preparations, e.g. intimate washing lotions or         intimate sprays;     -   foot-care preparations, e.g. foot baths, foot powders, foot         creams or foot balsams, special deodorants and antiperspirants         or callus-removing preparations;     -   light-protective preparations, such as sun milks, lotions,         creams or oils, sun-blocks or tropicals, pre-tanning         preparations or after-sun preparations;     -   skin-tanning preparations, e.g. self-tanning creams;     -   depigmenting preparations, e.g. preparations for bleaching the         skin or skin-lightening preparations;     -   insect-repellents, e.g. insect-repellent oils, lotions, sprays         or sticks; deodorants, such as deodorant sprays, pump-action         sprays, deodorant gels, sticks or roll-ons;     -   antiperspirants, e.g. antiperspirant sticks, creams or roll-ons;     -   preparations for cleansing and caring for blemished skin, e.g.         synthetic detergents (solid or liquid), peeling or scrub         preparations or peeling masks;     -   hair-removal preparations in chemical form (depilation), e.g.         hair-removing powders, liquid hair-removing preparations, cream-         or paste-form hair-removing preparations, hair-removing         preparations in gel form or aerosol foams;     -   shaving preparations, e.g. shaving soap, foaming shaving creams,         non-foaming shaving creams, foams and gels, preshave         preparations for dry shaving, aftershaves or aftershave lotions;     -   fragrance preparations, e.g. fragrances (eau de Cologne, eau de         toilette, eau de parfum, parfum de toilette, perfume), perfume         oils or perfume creams;     -   dental care, denture-care and mouth-care preparations, e.g.         toothpastes, gel toothpastes, tooth powders, mouthwash         concentrates, anti-plaque mouthwashes, denture cleaners or         denture fixatives;     -   cosmetic hair-treatment preparations, e.g. hair-washing         preparations in the form of shampoos and conditioners, hair-care         preparations, e.g. pretreatment preparations, hair tonics,         styling creams, styling gels, pomades, hair rinses, treatment         packs, intensive hair treatments, hair-structuring preparations,         e.g. hair-waving preparations for permanent waves (hot wave,         mild wave, cold wave), hair-straightening preparations, liquid         hair-setting preparations, hair foams, hairsprays, bleaching         preparations, e.g. hydrogen peroxide solutions, lightening         shampoos, bleaching creams, bleaching powders, bleaching pastes         or oils, temporary, semi-permanent or permanent hair colorants,         preparations containing self-oxidising dyes, or natural hair         colorants, such as henna or camomile.

An antimicrobial soap has, for example, the following composition:

-   -   0.01 to 5% by weight of a compound of formula (1)     -   0.3 to 1% by weight titanium dioxide,     -   1 to 10% by weight stearic acid,     -   soap base ad 100%, e.g. a sodium salt of tallow fatty acid or         coconut fatty acid, or glycerol.

A shampoo has, for example, the following composition:

-   -   0.01 to 5% by weight of a compound of formula (1),     -   12.0% by weight sodium laureth-2-sulfate,     -   4.0% by weight cocamidopropyl betaine,     -   3.0% by weight NaCl and     -   water ad 100%.

A deodorant has, for example, the following composition:

-   -   0.01 to 5% by weight of a compound of formula (1),     -   60% by weight ethanol,     -   0.3% by weight perfume oil, and     -   water ad 100%.

The invention relates also to an oral composition containing from 0.01 to 15% by weight, based on the total weight of the composition, of a compound of formula (1), and orally tolerable adjuvants.

Example of an oral composition:

-   -   10% by weight sorbitol,     -   10% by weight glycerol,     -   15% by weight ethanol,     -   15% by weight propylene glycol,     -   0.5% by weight sodium lauryl sulfate,     -   0.25% by weight sodium methylcocyl taurate,     -   0.25% by weight polyoxypropylene/polyoxyethylene block         copolymer,     -   0.10% by weight peppermint flavouring,     -   0.1 to 0.5% by weight of a compound of formula (1), and     -   48.6% by weight water.

The oral composition according to the invention may be, for example, in the form of a gel, a paste, a cream or an aqueous preparation (mouthwash).

The oral composition according to the invention may also comprise compounds that release fluoride ions which are effective against the formation of caries, for example inorganic fluoride salts, e.g. sodium, potassium, ammonium or calcium fluoride, or organic fluoride salts, e.g. amine fluorides, which are known under the trade name Olafluor.

The 4-aminopyrimidines of formula (1) used in accordance with the invention are also suitable for treating, especially preserving, textile fibre materials. Such materials are undyed and dyed or printed fibre materials, for example of silk, wool, polyamide or polyurethanes, and especially cellulosic fibre materials of all kinds. Such fibre materials are, for example, natural cellulose fibres, such as cotton, linen, jute and hemp, as well as cellulose and regenerated cellulose. Preferred suitable textile fibre materials are made of cotton.

The 4-aminopyrimidines according to the invention are suitable also for treating, especially imparting antimicrobial properties to or preserving, plastics such as, for example, polyethylene, polypropylene, polyurethane, polyester, polyamide, polycarbonate, latex etc. Fields of use therefor are, for example, floor coverings, plastics coatings, plastics containers and packaging materials; kitchen and bathroom utensils (e.g. brushes, shower curtains, sponges, bathmats), latex, filter materials (air and water filters), plastics articles used in the field of medicine such as, for example, dressing materials, syringes, catheters etc., so-called “medical devices”, gloves and mattresses.

Paper, for example papers used for hygiene purposes, may also be provided with antimicrobial properties using the 4-aminopyrimidines according to the invention.

It is also possible for nonwovens such as, for example, nappies/diapers, sanitary towels, panty liners, and cloths for hygiene and household uses, to be provided with antimicrobial properties in accordance with the invention.

The 4-aminopyrimidines of formula (1) are also used in washing and cleaning formulations such as, for example, liquid or powder washing agents or softeners.

The 4-aminopyrimidines of formula (1) can also be used especially in household and general-purpose cleaners for cleaning and disinfecting hard surfaces.

A cleaning preparation has, for example, the following composition:

-   -   0.01 to 5% of a compound of formula (1)     -   3.0% octyl alcohol 4EO     -   1.3% fatty alcohol C₈-C₁₀polyglucoside     -   3.0% isopropanol     -   water ad 100%.

In addition to preserving cosmetic and household products, the preservation of technical products, the provision of technical products with antimicrobial properties and use as a biocide in technical processes are also possible, for example in paper treatment, especially in paper treatment liquors, printing thickeners of starch or cellulose derivatives, surface-coatings and paints.

The 4-aminopyrimidines of formula (1) are also suitable for the antimicrobial treatment of wood and for the antimicrobial treatment of leather, the preserving of leather and the provision of leather with antimicrobial properties.

The compounds according to the invention are also suitable for the protection of cosmetic products and household products from microbial damage.

The following Examples illustrate, but do not limit, the present invention.

IMPLEMENTATION EXAMPLES General Work Procedure for Parallel Synthesis of 4-Aminopyrimidines Example 1

Preparation of 4-chloro-6-methyl-2-phenylpyrimidine

2.2 g of benzamidine hydrochloride (14.05 mmol) are reacted, in 10 ml of absolute EtOH, with 5.43 ml (14.05 mmol) of 20% sodium ethanolate solution and then condensed with 1.66 g of methyl acetoacetate (14.29 mmol) for 4 hours at 90° C.

The crude product is concentrated by evaporation and taken up in 30 ml of toluene.

4.31 g of phosphorus oxychloride (28.1 mmol) are added and the reaction mixture is heated at 120° C. for 3 hours. After cooling to 20° C., the excess is neutralised with sodium hydroxide solution, and the mixture is diluted with ethyl acetate and then washed with water and saturated sodium chloride solution.

The product solution is dried over sodium sulfate and concentrated by evaporation.

2.2 g of 4-chloro-6-methyl-2-phenylpyrimidine (77.7% of theory) are obtained.

Example 2 Reaction of 4-chloro-6-methyl-2-phenylpyrimidine with Monoamines

20.5 mg of 4-chloro-6-methyl-2-phenylpyrimidine (0.1 mmol) are heated with 3 equivalents of monoamines (0.3 mmol) in 0.5 ml of absolute dioxane at 100° C. for 20 hours. After cooling, the products are concentrated in vacuo, taken up in t-BuOH/water 4/1 and freeze-dried. The end products are analysed by LC-MS.

Example 3 Loading of Trityl Chloride Polystyrene Resin with N,N-bis(3-aminopropyl)methylamines and Reaction with 4,6-dichloro-2,5-diphenylpyrimidine

In each case, 50 mg of resin (1.29 mmol/g) are shaken in 1 ml of DMF with 94 mg of N,N-bis(3-aminopropyl)methylamine (0.645 mmol) at 25° C. for 3 hours. The resin is filtered off and washed with DCM, MeOH, THF, MeOH and DCM and dried in vacuo.

The resin is shaken in 1 ml of DMF with 0.194 g of 4,6-dichloro-2,5-diphenylpyrimidine (0.645 mmol) and 90 μl of triethylamine (0.645 mmol) at 25° C. for 3 hours.

The resin is filtered off and washed with DCM, MeOH, THF, MeOH, DCM and MeOH and dried in vacuo.

Example 4 Parallel Reaction of 4-amino-6-chloro-1,5-diphenylpyrimidine-TCP Resins with Various Boronic Acids and Splitting Off

The resin is heated with 126.1 g of caesium carbonate (6 eq., 0.387 mmol) and 300 μL of a toluene solution of 0.1 eq. of a palladium catalyst (WO 01/16057) at 95° C. for 15 minutes. After adding 3 eq. of a boronic acid, dissolved in 700 μl of toluene solution, the mixture is heated at 90° C. for 1 hour.

After cooling, the resin is filtered off and washed with DMF, MeOH, THF, MeOH and DCM and dried in vacuo.

The products are split off using 1.5 ml of a 5% TFA/DCM solution at room temperature for 3 hours. The resin is then washed with 1 ml of DCM and 1 ml of MeOH, and the combined solutions are concentrated to dryness by evaporation. The end products are analysed by LC-MS.

Example 5 Preparation of 4-chloro-6-methyl-2-tolylpyrimidine

2.5 g of 4-methyl-benzamidine hydrochloride (14.65 mmol) are reacted in 10 ml of absolute EtOH with 5.66 ml of a 20% solution of sodium ethanolate (14.65 mmol) and then condensed with 1.73 g of methyl acetoacetate (14.88 mmol) at 90° C. for 4 hours. The crude product is concentrated by evaporation and taken up in 30 ml of toluene. 6.74 g of phosphorus oxychloride (44.0 mmol) are added and the reaction mixture is heated at 120° C. for 3 hours. After cooling to 20° C., the excess is neutralised with sodium hydroxide solution, and the mixture is diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution and then with water. The product solution is concentrated by evaporation and separated by column chromatography (hexane/EE: 5/1). 2.1 g of 4-chloro-6-methyl-2-tolylpyrimidine (66.5% of theory) are obtained.

NMR: 1H (ppm in DMSO): 2.4, s, 3H; 2.55, s, 3H; 7.3, d, 2H; 7.5, s, 1H; 8.25, d, 2H

Example 6 Reaction of 4-chloro-6-methyl-2-(4-methyl)-phenylpyrimidine with Monoamines

21.9 mg of 4-chloro-6-methyl-2-(4-methyl)-phenylpyrimidine (0.1 mmol) are heated with 3 eq. of monoamines (0.3 mmol) in 0.5 ml of absolute dioxane at 100° C. for 20 hours. After cooling, the products are concentrated in vacuo, taken up in t-BuOH/water 4/1 and freeze-dried. The end products are analysed by LC-MS.

Example 7 Reaction of 4-chloro-6-methyl-2-(4-methyl)-phenylpyrimidine with Octylamine

1.36 g of 4-chloro-6-methyl-2-(4-methyl)-phenylpyrimidine (6.23 mmol) are heated with 886 mg of octylamine (6.85 mmol) and 2.58 g of potassium carbonate (18.68 mmol) in 10 g of dioxane at 100° C. for 48 hours. After cooling, the product is taken up in 100 ml of ethyl acetate and washed with sodium hydroxide solution 0.5 mol/l, saturated sodium hydrogen carbonate solution and water. The product is concentrated in vacuo, taken up in t-BuOH/water 4/1 and freeze-dried.

1.92 g of 4-chloro-6-methyl-2-(4-methyl)-phenylpyrimidine (6.15 mmol, 98.7% of theory) are obtained.

The end product is analysed by NMR, GC-MS and GC.

NMR 1H (ppm in DMSO): 0.9, t, 3H; 1.25, m, 12H; 1.55, m, 2H; 2.25, s, 3H; 2.3, s, 3H; 6.4, s, 1H; 7.1, m, 1H; 7.2, d, 2H; 8.2, d, 2H; (m/z=311);

GC: 95% purity

Example 8 Preparation of 4-chloro-2-isopropyl-6-methylpyrimidine

76.1 g of 2-isopropyl-6-methyl-4-pyrimidinol [2814-20-2] (500 mmol) are dissolved in 300 ml of toluene at 90° C. 80.5 g of phosphorus oxychloride (525 mmol) are added dropwise thereto at from 90 to 103° C., and the reaction mixture is heated at 110° C. for 2 hours. After cooling to 20° C., the reaction mixture is adjusted to pH 8 using 4M sodium hydroxide solution, with cooling. The aqueous phase is separated off and extracted with 100 ml of toluene. The combined organic phases are washed three times with 100 ml of water each time and dried at RT under 2 mbar. 89.7 g (105%; contains toluene) are obtained.

Example 9 Preparation of 4-dodecylamino-2-isopropyl-6-methylpyrimidine (Compound of Formula (93)

79.2 g of 4-chloro-2-isopropyl-6-methylpyrimidine (464.1 mmol) are heated in 100 ml of dioxane at 100° C. A heated solution of 189.3 g of dodecylamine (1021 mmol, 2.2 eq) in 30 ml of dioxane is added dropwise thereto over the course of 2 hours, and the reaction mixture is further heated for 2 hours at 100° C. and for 9 hours at 109° C. After cooling, 400 ml of ethyl acetate and 150 ml of 4M sodium hydroxide solution (600 mmol) are added thereto and the mixture is stirred at 50° C. for 10 minutes. The lower, aqueous phase is discarded, the organic phase is washed with 300 ml of water, and 10 ml of saturated NaCl solution are added thereto. The organic phase is separated off and concentrated, and the excess dodecylamine is distilled in vacuo up to a bath temperature of 160° C. 136.1 g (91.8%); GC purity: 98%

NMR 1H (ppm in CDCl₃): 0.7, t, 3H; 1.1, m, 24H; 1.4, m, 2H; 2.15, s, 3H; 2.75, Q, 1H; 3.05, m, 2H; 4.9, s, 1H; 5.8, s, 1H

Example 10 Determination of the Minimum Inhibitory Concentration (MIC Value) in Microtitre Plates

Nutrient Medium:

Casein/soymeal peptone broth for preparation of pre-cultures of test bacteria and yeast

Examples of Test Organisms:

Bacteria:

-   -   Pseudomonas aeruginosa CIP A-22 (=PA)     -   Escherichia coli NCTC 8196 (=EC)     -   Staphylococcus aureus ATCC 9144 (=SA)     -   Candida albicans ATCC 10231 (=CA)

Procedure:

The test substances are pre-dissolved in dimethyl sulfoxide (DMSO) and tested in a dilution series of 1:2.

Bacteria and yeast are cultured overnight in CASO broth.

All the test organism suspensions are adjusted to an organism count of 1-5×10⁶ CFU/ml using 85% sodium chloride solution.

The test substances are pre-pipetted into microtitre plates in amounts of 8 μl per well.

The pre-adjusted organism suspensions are diluted 1:100 in CASO broth and are added in amounts of 192 μl per well to the test substances.

The test batches are incubated for 48 hours at 37° C.

The incubation, the growth is determined on the basis of the turbidity of the test batches (optical density) at 620 nm in a microplate reader.

The minimum inhibitory concentration (MIC value) is the concentration of substance at which (compared to the growth of the control) an appreciable inhibition of growth (≦20% growth) of the test organisms is observed.

Three microtitre plates are used for each test organism and substance concentration. All the substances are tested in duplicate.

The microbiological test results are compiled in Table 2:

TABLE 2 Comp. of Purity [%] Purity [%] MIC MIC MIC MIC formula 254 nm 280 nm SA EC PA CA 3 64 72 7.5 15 >120 7.5 4 37 96 7.5 30 >120 15 5 83 97 7.5 >120 >120 >120 6 92 97 7.5 60 >120 >120 7 43 48 15 15 >120 30 8 82 93 30 30 >120 120 9 94 98 15 15 >120 30 10 49 59 15 30 >120 30 11 75 89 7.5 15 >120 7.5 12 95 97 7.5 3.75 7.5 7.5 13 94 99 15 15 >120 30 14 91 97 15 3.75 30 15 15 91 98 15 >120 >120 >120 16 42 44 7.5 15 >120 15 17 39 43 15 30 >120 15 18 42 51 30 30 120 60 19 64 70 7.5 15 >120 8 20 63 77 15 30 >120 15 21 70 82 7.5 <3.75 7.5 <3.75 22 51 65 15 15 >120 7.5 23 67 82 15 7.5 30 7.5 24 95 97 30 15 30 30 25 88 96 >120 60 >120 120 26 81 90 60 60 >120 >120 27 88 93 30 30 >120 60 28 86 93 <3.75 >120 >120 >120 29 61 62 15 30 >120 30 30 85 72 60 30 >120 15 31 45 42 60 >120 >120 120 32 69 64 60 120 >120 60 33 94 93 30 >120 >120 60 34 89 89 7.5 120 >120 30 35 92 88 15 30 120 30 36 82 73 7.5 15 60 7.5 37 82 66 7.5 15 >120 7.5 38 56 34 <3.75 7.5 >120 <3.75 39 67 46 <3.75 30 >120 15 40 43 44 60 >120 >120 120 41 81 77 30 >120 >120 60 42 91 92 <3.75 120 >120 30 43 72 68 60 >120 >120 120 44 88 84 120 >120 >120 120 45 82 83 60 >120 >120 120 46 88 88 120 >120 >120 120 47 72 67 120 >120 >120 >120 48 81 85 30 >120 >120 60 49 92 84 120 >120 >120 >120 50 84 86 120 >120 >120 >120 51 77 73 30 >120 >120 >120 52 88 91 30 >120 >120 120 53 87 89 60 >120 >120 120 54 90 91 15 >120 >120 120 55 85 87 120 >120 >120 >120 56 87 84 60 >120 >120 120 57 99 99 60 >120 >120 120 58 58 78 15 120 >120 60 59 34 64 15 60 >120 60 60 46 32 120 >120 >120 120 61 90 87 30 120 >120 120 62 66 61 60 120 >120 120 63 99 95 15 30 >120 60 64 80 80 7.5 30 >120 15 65 96 92 30 60 >120 15 66 90 95 <3.75 30 >120 30 67 48 44 7.5 30 >120 7.5 68 37 38 15 30 >120 15 69 64 79 <3.75 30 >120 7.5 70 71 82 <3.75 15 >120 7.5 71 88 88 7.5 15 >120 7.5 72 79 52 7.5 15 >120 7.5 73 90 96 <3.75 7.5 >120 <3.75 74 79 39 <3.75 7.5 >120 <3.75 75 92 89 7.5 15 >120 7.5 76 97 95 15 60 >120 30 77 86 90 7.5 60 >120 15 78 90 94 <3.75 7.5 >120 <3.75 79 92 95 <3.75 <3.75 >120 <3.75 80 54 50 <3.75 7.5 >120 7.5 81 40 42 <3.75 <3.75 >120 <3.75 82 67 84 <3.75 15 >120 7.5 83 77 72 <3.75 7.5 >120 <3.75 84 93 91 15 15 >120 7.5 85 83 80 15 7.5 <120 7.5 86 92 92 15 15 <120 7.5 87 95 94 15 15 <120 7.5 88 95 94 15 15 <120 7.5 89 92 90 <3.75 <3.75 >120 <3.75 90 54 33 7.5 15 >120 <3.75 91 89 95 30 30 >120 15 92 52 48 <3.75 15 >120 7.5 93 40 39 <3.75 15 >120 7.5 94 65 80 <3.75 15 >120 7.5 95 82 83 15 30 >120 15 96 78 85 15 30 >120 15 97 31 26 7.5 15 >120 15 98 79 60 15 15 >120 15 99 93 90 15 15 >120 30 100 71 59 15 15 >120 15 101 87 78 7.5 7.5 >120 7.5 102 49 25 7.5 30 >120 15 103 89 89 15 60 >120 30 104 54 41 <3.75 7.5 >120 7.5 105 33 38 7.5 15 >120 7.5 106 65 75 <3.75 15 >120 15 107 80 82 7.5 15 >120 15 108 87 96 30 >120 >120 >120 109 87 87 15 60 >120 30 110 90 94 60 >120 >120 120 111 94 92 7.5 120 >120 60 112 87 90 15 120 >120 30 113 92 85 7.5 120 >120 30 114 41 28 15 >120 >120 30 115 93 96 7.5 >120 >120 120 116 58 46 7.5 60 >120 15 117 39 40 15 120 >120 30 118 54 70 7.5 60 >120 15 119 82 87 7.5 >120 >120 120 120 42 35 30 120 >120 30 121 87 90 30 >120 >120 >120 122 78 87 30 >120 >120 120 123 68 73 120 >120 >120 >120 124 93 96 60 120 >120 60 125 93 93 120 >120 >120 120 126 87 86 120 >120 >120 120 127 65 69 60 >120 >120 60 128 46 52 120 >120 >120 120 129 58 69 120 >120 >120 120 130 82 83 120 >120 >120 >120 131 73 74 120 >120 >120 >120 132 88 90 60 >120 >120 >120 133 94 93 15 >120 >120 >120 134 100 89 7.5 >120 >120 120 135 92 91 60 120 >120 30 136 92 92 7.5 >120 >120 60 137 49 44 15 30 >120 15 138 41 41 30 60 >120 30 139 50 66 7.5 60 >120 30 140 100 80 15 >120 >120 120 141 74 71 120 >120 >120 >120 142 100 83 30 >120 >120 120 143 84 79 >120 >120 >120 120 144 62 54 60 >120 >120 120 145 43 39 >120 >120 >120 120 146 34 35 >120 >120 >120 120 147 61 73 60 >120 >120 120 148 72 70 120 >120 >120 >120

Example 11: Agar incorporation test CG128e Medium: Casein/soymeal peptone agar (Merck) *Sabouraud 4% glucose agar (Merck) Diluent: Sterile 0.85% NaCl solution Incubation: 24 hours at 37° C. *3 days at 28° C. Test solution: 1% stock solutions of all the test substances are prepared in a suitable solvent and diluted in serial dilutions to end concentrations of from 1000 ppm to 10 ppm.

Test Principle:

0.3 ml of each dilution step is mixed with 15 ml of nutrient medium while the latter is still liquid. After the nutrient medium has solidified, 10 μl of each of the following organism dilutions of the test strains in 0.85% NaCl solution are spotted onto the agar medium:

Microorganisms Used:

Staphylococcus aureus ATCC 6538 Staphylococcus aureus ATCC 9144 Staphylococcus epidermidis Corynebacterium xerosis* ATCC 12228 ATCC 373 C. minutissimum ATCC 23348 Propionibacterium acnes (*) ATCC 6919 Escherichia coli NCTC 8196 Escherichia coli ATCC 10536 Proteus vulgaris ATCC 6896 Klebsiella pneumoniae ATCC 4352 Salmonella choleraesuis ATCC 9184 Pseudomonas aeruginosa ATCC 15442 Candida albicans ATCC 10231 Aspergillus niger ATCC 6275

The plates are incubated at 37° C. for 24 hours (A. niger at 28° C. for 3 days) and then the highest dilution (lowest concentration) of the test substance at which growth is just no longer discernible (corresponds to the MIC) is determined. The results are shown in Table 3.

TABLE 3 Compound of formula Microorganism (36) (89) (93) Staphylococcus aureus ATCC 6538   120 7.5 3.75 Staphylococcus aureus ATCC 9144   120 7.5 3.75 Staphylococcus epidermidis ATCC 12228 >120 120 3.75 Corynebacterium xerosis* ATCC 373    60 3.75 1.88* C. minutissimum ATCC 23348    30 3.75 1.88 Propionibacterium acnes (*) ATCC 6919    60 3.75 3.75 (*) Escherichia coli NCTC 8196   120 120 120 Escherichia coli ATCC 10536 >120 >120 120 Proteus vulgaris ATCC 6896 >120 60 >120 Klebsiella pneumoniae ATCC 4352    60** >120 60 Salmonella choleraesuis ATCC 9184 >120 >120 120 Pseudomonas aeruginosa ATCC 15442 >120 >120 >120 Candida albicans ATCC 10231 >120 >120 >120 Aspergillus niger ATCC 6275 >120 >120 >120

Example 12 “Microbicidal Activity” Suspension Test CG 161/EN1040

Test Method:

Nutrient Medium:

-   -   Casein/soymeal peptone broth for preparation of pre-cultures of         test bacteria

Examples of Test Organisms:

-   -   Staphylococcus aureus ATCC 6538     -   Escherichia coli ATCC 10536     -   Actynomyces viscosus ATCC 43146

Procedure:

The test substances are dissolved in dimethyl sulfoxide (DMSO) and tested in a concentration of 120 μg/ml.

Bacteria are incubated overnight in CASO broth and adjusted to an organism count of 1-5×10⁵ CFU/ml using 0.85% sodium chloride solution.

The test substances are pre-pipetted into microtitre plates in amounts of 8 μl per well.

The adjusted test organism suspensions are added in amounts of 192 μl per well to the test substances and mixed. After defined contact times, the test batches are mixed, an aliquot is withdrawn and diluted in several steps in a dilution series of 1:10 in a suitable inactivation medium.

The test plates are incubated for 24 hours at 37° C. After incubation, the growth is determined on the basis of the turbidity of the test batches (optical density) at 620 nm in a microplate reader.

On the basis of the number of steps in the dilution series that exhibit growth, the reduction in the test organism concentration is determined in powers of ten (log value).

One microtitre plate is used for each test organism.

All the substances are tested in duplicate.

The results (log reduction) are shown in Table 4:

TABLE 4 Compound of formula (93) (93) (89) (89) Organism Contact time 0.12% 120 ppm 0.12% 120 ppm S. aureus  5 min >5 1.4 <1 S. aureus 30 min >5 3.8 1.7 E. coli  5 min >5 >5 4.6 E. coli 30 min >5 >5 >5 A. viscosus  5 min >5 2 4.9 3.9 A. viscosus 30 min >5 4 >5 4.3

Example 13 Determination of the Minimum Inhibitory Concentration (MIC Value) in Microtitre Plates

Nutrient medium and test procedure correspond to Example 10.

As test organisms there are used:

-   -   Staphylococcus aureus ATCC 6538     -   Escherichia coli ATCC 10536     -   Actynomyces viscosus ATCC 43146

Microbiological test results are compiled In Table 5:

TABLE 5 Comp. of Purity [%] Purity [%] formula 254 nm 280 nm MIC SA MIC EC MIC AV 149 91 89 120 >120 15 150 87 88 120 >120 60 151 88 86 120 >120 15 152 91 83 30 >120 15 153 89 85 120 >120 30 154 94 85 120 120 30 155 85 81 30 30 7.5 156 86 82 7.5 15 <3.75 157 62 63 15 >120 <3.75 158 86 92 >120 >120 7.5 159 89 91 120 >120 30 160 88 92 120 >120 15 161 87 92 120 >120 30 162 67 88 120 >120 30 163 67 66 >120 >120 60 164 85 92 120 >120 30 165 81 92 >120 >120 30 166 68 75 >120 >120 30 167 92 89 120 120 15 168 72 73 >120 >120 15 169 87 83 >120 >120 30 170 77 85 >120 >120 15 171 86 81 120 >120 30 172 87 72 60 >120 15 173 69 67 60 60 15 174 66 87 120 >120 60 175 69 64 120 120 30 176 82 57 30 30 7.5 177 87 92 120 >120 30 178 77 69 120 120 30 179 77 85 120 120 30 

1. A method for the antimicrobial treatment of a surface, which comprises contacting said surface with a 4-aminopyrimidine of formula

R₁ is biphenyl or C₆-C₁₀aryl which is unsubstituted or substituted by halogen, C₁-C₅alkyl, C₁-C₅alkoxy or by amino; R₂ is biphenyl or C₆-C₁₀aryl which is unsubstituted or substituted by halogen, C₁-C₅alkyl, C₁-C₅alkoxy or by amino; R₃ is phenyl which is unsubstituted or substituted by one or more halogen atoms; R₄ is hydrogen; R₅ is C₁-C₂₀alkyl substituted by N(R″)R′″ which alkyl is either further unsubstituted or further substituted by a heterocyclic radical or uninterrupted or interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; or R₄ and R₅, together with the nitrogen atom linking them, form a radical of

R′ is hydrogen; or C₁-C₃alkyl; R″ and R′″ are each independently of the other hydrogen; C₁-C₅alkyl; or hydroxy-C₁-C₅alkyl; X is

R″″ is hydrogen; C₁-C₄alkyl; or heteroaryl-C₁-C₄alkyl; and n₁ and n₂ are each independently of the other from 1 to
 8. 2. A method according to claim 1, wherein R₅ is R″R′″N—C₁-C₂₀alkyl which is uninterrupted or interrupted by one or more —O— or

groups or by a bivalent heterocyclic radical; R′ is hydrogen; or C₁-C₅alkyl; R″ and R′″ are each independently of the other hydrogen; or methyl.
 3. A method according to claim 1, wherein R₅ is R″R′″N—C₁-C₂₀alkyl which is uninterrupted or interrupted by


4. A method according to claim 1, wherein R₅ is R″R′″N—C₅-C₂₀alkyl which is uninterrupted or interrupted by one or more —O— or

groups; R′ is hydrogen; or C₁-C₅alkyl; and R″ and R′″ are each independently of the other hydrogen; or methyl.
 5. A method according to claim 4, wherein R₅ is R″R′″N—C₅-C₂₀alkyl; and R″ and R′″ are each independently of the other hydrogen; or methyl.
 6. A method according to claim 1, wherein R₄ is hydrogen.
 7. A method according to claim 1, wherein the compound of formula (1) is used in the antimicrobial treatment, deodorisation and disinfection of the skin, mucosa and hair.
 8. A method according to claim 1, wherein the compound of formula (1) is used in the treatment of textile fibre materials.
 9. A method according to claim 1, wherein the compound of formula (1) is used in preservation.
 10. A method according to claim 1, wherein the compound of formula (1) is used in washing and cleaning formulations.
 11. A method according to claim 1, wherein the compound of formula (1) is used in imparting antimicrobial properties to, and preserving, plastics, paper, nonwovens, wood or leather.
 12. A method for the antimicrobial treatment of a surface according to claim 1, which comprises contacting said surface with a preparation containing 0.01 to 15% by weight of a 4-aminopyrimidine of formula (1). 